Blood Safety and Availability

Introduction

I. Definition of the Prevention Area

Blood transfusion is an essential part of modern medical care. Inadequate and unsafe blood supply causes avoidable deaths and transmits infectious diseases, including HIV, hepatitis B and C, and syphilis. Preventing transfusion of unsafe blood through improved screening of donors and testing processes, and increasing participation of voluntary, non-remunerated blood donors (VNRD) can significantly reduce the spread of HIV. A safe blood supply also protects the health of people living with HIV by ensuring they do not receive blood transfusions contaminated with such blood-borne infections as hepatitis B or C.

II. Epidemiological Justification for the Prevention Area

Transfusion of blood infected with HIV is one of the most effective modes of transmission of the virus. The risk of acquiring HIV infection following transfusion with HIV-positive blood has been estimated to be as high as 70 to 91 percent. Implementing a national testing and donor selection algorithm that establishes the tests to be used significantly reduces the potential of transmitting infectious diseases. In a 2009 study of Kenya's screening algorithm, even highly rigorous nucleic acid testing (NAT) failed to outperform the national algorithm in detecting units of blood infected with HIV.

Approximately 80 percent of the world's supply of safe blood goes to 20 percent of the population, mostly in developed countries. There is a chronic shortage of safe blood in sub-Saharan Africa where, in some areas, hemorrhage leading to blood loss accounts for up to 44 percent of maternal deaths and approximately half of transfused blood goes to children under five years of age with anemia due to malaria or malnutrition. Africa has the lowest blood donation rate per capita in the world, so often family members are asked to provide blood for the person in need of transfusion. These "replacement donors" are at greater risk for transmissible diseases than are VNRD, particularly repeat donors. In addition, blood shortages may lead to release of blood for transfusion before testing is completed, further adding to the potential for disease transmission. These problems are exacerbated in regions with high endemic rates of transmissible diseases. Therefore, it is important to recruit potential donors who are least likely to harbor transfusion-transmissible infectious agents.

The World Health Organization (WHO) and the Joint U.N. Programme on HIV/AIDS (UNAIDS) recommend VNRD as the foundation of a safe blood supply. Because VNRD donate motivated by altruism rather than by financial or institutional pressure, they are more likely to meet the medical selection criteria for safe donors, to disclose any known possibility of risk exposure, and to donate blood regularly and at properly spaced intervals. However, many countries are faced with misconceptions and fear of testing, which results in a limited number of VNRD. Countries are challenged to find creative recruitment methods to combat misconceptions about blood donation and to motivate the public to donate. Many countries have targeted youth donors under the age of 25 because youth have the lowest HIV prevalence, and blood donor mobilization activities provide opportunities to promote healthier lifestyle choices that mitigate risk over time. Some countries have created social and sporting clubs for blood donors to improve retention and create an identity and pride regarding blood donation.

III. Core Programmatic Components

The primary objective of international blood safety programs such as that of WHO is reducing transmission of infectious diseases through blood transfusion and collecting an adequate supply of blood to meet the needs of the country. This may include the following:

Establishing supportive policies and legal frameworks for the national blood program

Strengthening the infrastructure of the national blood transfusion service

Increasing blood collections from VNRD

Establishing a comprehensive quality assurance system for the blood program, covering the entire transfusion process from donor recruitment, blood collection, production of blood components, testing, storage, transport, and maintenance of the cold chain, to transfusion to the patient

Improving the capacity of human resources through a structured training and education program

A key aspect of improving blood safety is testing for transmissible diseases. However, up to 13 million units, or about 40 percent of the global blood supply, are not screened for all relevant transfusion-transmissible infections. There are several reasons for this, including 1) erratic stream of blood screening supplies; 2) erratic power supply; 3) lack of trained personnel; 4) use of outdated laboratory supplies; 5) poor, out-of-date testing methods that cannot ensure safety (e.g., that do not detect recent HIV infection); 6) cost of reagents; and 7) failure to complete testing when physicians request "fresh blood" to be transfused immediately after collection from the donor, which may not allow adequate time to complete the testing process.

IV. Current Status of Implementation Experience

In a 2007 WHO survey of 148 countries, 41 reported that they were not able to test all donated blood for HIV, hepatitis B, hepatitis C, and syphilis. WHO estimates that the lack of effective screening continues to result in up to 16 million new infections with hepatitis B, 5 million new infections with hepatitis C, and 160,000 cases of HIV infection every year. Effective blood safety interventions could reduce the transmission of HIV and other infections. Blood safety initiatives could also protect investments in prevention of mother-to-child transmission of HIV (PMTCT) programming by optimizing chances that PMTCT clients do not die during childbirth because of lack of blood.

Broad uptake of HIV testing and counseling holds promise for increasing the proportion of potential donors who know their HIV status, making it an important complementary component of PEPFAR's prevention programming. In addition, blood donor recruitment campaigns present an opportunity for HIV prevention messaging.

Over the past five years, several developing countries have made significant improvements to their national blood programs, including renovation of facilities, increased blood collection, staff training, and implementation of monitoring and evaluation systems. However, additional work is needed to ensure that all blood is screened for infectious diseases, that blood is appropriately used according to nationally established guidelines, and that an adequate supply of blood is available to meet the needs of each country. In addition, several exciting new technologies are evolving, including pathogen inactivation, which should be assessed for feasibility and cost-effectiveness in the developing world. Going forward, the foundation of a safe and adequate blood supply will be a pool of low-risk, VNRD, a stringent health history screening process, and a national testing algorithm.

A cross-sectional, nationally representative AIDS survey in 2007 was used to compare voluntary blood donors with family replacement donors (FRD) in Kenya. Nearly 18,000 men and women aged 15 to 64 years participated, providing blood samples that were tested for sexually transmitted infections. Approximately 2 percent (445) had donated blood in the year before the survey. Among them, the majority reported voluntary donation (64 percent). Volunteer donors tended to be younger and wealthier than FRDs and reported lower levels of sexual activity and fewer sex partners in the year before the survey. HIV prevalence was 2.6 percent among voluntary donors and 7.4 percent among FRDs (p = 0.07); herpes simplex virus 2 prevalence was 20 percent and 40 percent, respectively (p = 0.001). Voluntary donors comprised 6.5 of every 10 blood donations in 2007, up from 2 in 10 in 2001. Efforts are needed, however, to reduce reliance on FRDs, who are generally subject to less stringent screening practices and thus increase the risk of TTI.

Kenya began implementing measures to reduce transfusion-transmitted infections (TTIs) in its national blood supply in 2001. Donations are voluntary and non-remunerated, and donors undergo a health exam and answer a behavioral risk screening questionnaire. Donations are also screened using fourth-generation p24 antigen and HIV 1 and 2 antibody tests (ELISA). Such screening is not likely to detect infections within the window period before seroconversion, which is approximately 18 days. Nucleic acid testing (NAT) can reduce this window period to about 11 days. To estimate the number of window period infections entering the Kenyan blood supply, over 12,000 specimens from six national collection centers were tested for HIV using NAT. Any additional positive HIV donations in this sample would be attributable to the limitations of the fourth-generation screening tests. NAT retesting found no additional HIV infections, indicating that ELISA screening can significantly reduce HIV in the nation's blood supply, even in a setting with a generalized HIV epidemic. Because NAT costs 3 to 10 times more than ELISA, low-resource countries should carefully weigh the advantages and costs of using NAT.

This paper presents the first published modeling estimates of transfusion-transmitted infections (TTIs) in 45 sub-Saharan African countries. Despite a lack of data for 28 countries, the authors used available data, multiple assumptions, and applied statistical techniques to obtain rough risk estimates. With the current rate of 2 million annual transfusions in the region, the risk of infection with one unit of blood is 1.0 in 1,000 for HIV, 4.3 in 1,000 for hepatitis B, and 2.5 in 1,000 for Hepatitis C, resulting in nearly 16,000 TTIs. If the total estimated 6.65 million needed transfusions took place each year, the total annual TTIs would increase to nearly 52,000. Country-level data for 16 countries with more complete data find risks ranging from 7 HIV infections per 100,000 donations in South Africa to 1,096 hepatitis C infections per 100,000 donations in Gabon. A more thorough understanding of TTI risks can help countries develop appropriate responses. Because the disease burden of TTI is so high, the authors "reiterate the need for increased support from the global community to address transfusion-associated risks in the region."

This case report documents the rare event of HIV transmission via blood transfusion in the United States. After testing negative for HIV, a regular donor's blood was transfused to two patients. On repeat donation several months later, this donor's blood tested positive. Thus, the first blood donation took place during the window period, before the donor seroconverted. One recipient of the infected blood died due to underlying disease, and the second was indeed infected with HIV. The authors estimate that if 16 million blood donations take place annually in the United States, there are likely to be 11 infectious donations, resulting in 20 infected blood components. The questionnaire given to potential blood donors screens high-risk people out of the donation process. In this case study, the infected donor admitted to not answering truthfully to the screening questions. People who donate blood must answer accurately for the screening mechanism to work, thus reducing the risk of such window period infections entering the blood supply.

Although voluntary, regular, non-remunerated blood donors (VNRD) form the "backbone" of a healthy blood supply, most transfusions in sub-Saharan Africa are done through family replacement donations. In some countries, as much as 70 percent of the blood supply comes through such donors; voluntary donors were found to represent less than half of blood donors in 15 of 38 countries in one study. VNRD tend to be male and younger, and the authors describe successful strategies for recruiting and retaining such donors in Ghana and Zimbabwe. The review includes estimates of HIV, hepatitis B, and hepatitis C prevalence among repeat donors and first-time donors for 15 countries whose blood supply is comprised primarily of VNRD. The high prevalence of infectious disease in the region necessitates a strong blood screening program. This is a significant challenge, however, given infrastructure, financing, and cultural constraints in the region. The authors state that "more effort is required in the drive for education, motivation, and recruitment of regular donors," and conclude that collaborating with international partners may be the key to making it happen.

This document resulted from a global consultation meeting held in Melbourne, Australia, in 2009 that reviewed current barriers to safe global blood supply and identified ways to help countries reach the goal of 100 percent voluntary, non-remunerated blood donation. Country-specific examples illustrate the key issues and challenges of implementing such a policy, such as the role of the government and raising and maintaining public awareness. The document includes a copy of the Melbourne Declaration, which calls on WHO member states to achieve 100 percent voluntary, non-remunerated blood donations by 2020, and a checklist for action to achieve this.

This report looks both globally and regionally at the obstacles to universal access to safe blood transfusion. It then describes the key elements of eight strategies and approaches to help reach this goal. These include achieving totally voluntary, non-remunerated blood transfusion; universal access to safe blood donation; optimal use of donated blood; work force development; and developing quality transfusion management systems. The report also outlines WHO's Global Strategic Plan for Universal Access to Safe Blood Transfusion, 2008-2015 and lays out recommendations for WHO, national health authorities, and national or regional blood transfusion services (BTS).

This review found that the cost of voluntary blood donation at centralized collection centers is up to eight times higher than replacement collection at the hospital level, raising concerns about the sustainability of the centralized model in resource-poor settings. In practice, many countries incorporate elements of national coordination into locally based collection services and also use a variety of funding models according to local circumstances. The review cites sub-Saharan African examples of innovative strategies to collect and efficiently utilize donated blood. It also highlights the need for more data on the cost-effectiveness of hybrid strategies and research into their replicability in other countries.

Given the high costs of protecting a nation's blood supply, country budget constraints, and high levels of HIV, these researchers model multiple scenarios to understand whether levying user fees on blood recipients is a feasible way of financing blood transfusion services (BTS) in sub-Saharan Africa. The authors first undertake a literature review and detail the BTS in Côte d'Ivoire, Mozambique, and Zimbabwe, including financing. BTS expenditures were estimated at 0.8 percent of total public health expenditure in Côte d'Ivoire, 1.5 percent in Zimbabwe, and, for comparison purposes, 0.5 percent in England. Different scenarios are posed for collecting user fees, including three institutional funding options (fully central budget-funded, fully hospital-funded, or mixed) and five patient payment options. The authors present strengths and weaknesses of each scenario, concluding that there is a "limited role" for user fees in these settings. They summarize five key lessons learned from the costing exercise for program planners and donors to consider.

This study compiles the findings of numerous studies comparing infectious disease markers in blood from paid versus volunteer donors and finds that there is an association between paid donation and higher prevalence of donor HIV, hepatitis B and C, and syphilis infection as well as higher incidence of transfusion-transmitted infections (TTIs). However, the author acknowledges that many of the studies were small, not well controlled, and lacked statistical significance testing. Although it can be difficult to eliminate reliance on paid blood donors, the author writes, educational programs and government policies have helped overcome economic and cultural barriers to 100 percent voluntary, non-remunerated blood donation in many countries.

This paper describes the extremely challenging conditions under which Afghanistan's blood supply system health professionals operate. The country has a nationalized blood banking system comprising the Central Blood Bank of Kabul as well as 18 other branches in Kabul and throughout the country. However, over two decades of armed conflict have severely disrupted the system. Staff lack training in blood banking and transfusion medicine and face shortages of basic equipment and supplies, even water and electricity. The study makes recommendations to build on the existing basic infrastructure and dedicated staff by improving facilities and equipment, promoting voluntary blood donation, enhancing blood collection and processing procedures, and boosting training and education.

This study looks at blood donors with a confirmed positive HIV result who were invited for postdonation counseling. The information obtained during the session was then compared with that collected from the donors' answers to the predonation questionnaire and in the face-to-face interview. The postdonation interview revealed useful additional information about donor behavior and provided feedback on the efficacy of the predonation interview and questionnaire. Interviewees often lacked an understanding of the window period for HIV infection, evaded questions about concurrent partners, and were inconsistent in condom use. The open-ended nature of the questions in a postdonation interview highlights the need for counseling skills training for donor staff.

National Blood Service Zimbabwe has grappled with a host of difficulties caused by political instability, record levels of inflation, and shortages of funds, basic commodities and fuel, according to this paper. In the decade to 2008, blood collections fell and HIV seroprevalence among donors rose, but the system was able to maintain its record of 100 percent blood collection from voluntary, non-remunerated donors and 100 percent testing of donated blood. The service also improved its quality management system.

This article provides an overview of blood safety in developing countries and uses data from Tanzania to illustrate the increased risk of transfusion-transmitted infections (TTIs) from voluntary non-remunerated blood donors (VNRD) versus relative blood donors. It argues that a safe blood supply is an essential element of safe motherhood, as pregnancy-related bleeding complications are a significant cause of sudden death among women in developing countries. Safe blood can also reduce infant mortality associated with malnutrition, malaria, and worm infestation, as well as the transmission of HIV and other diseases, the authors write, but only within a wider context of political commitment and adequately trained health care workers.

This paper examines the paradox of sub-Saharan Africa's great need for blood transfusion (anemia is common, especially among women and children) and lack of access to a safe and reliable supply, given that blood-borne diseases such as HIV and hepatitis are prevalent. While most countries in the region have a transfusion policy, less than half consistently apply it, and the World Health Organization (WHO)-recommended strategy of promoting voluntary, non-remunerated blood donation has failed the thrive in many countries. The lack of testing, preparation of blood components, and inappropriate clinical use of blood all contribute to blood safety remaining a serious issue for sub-Saharan Africa.

The development of pathogen inactivation represents a paradigm shift for blood safety, the author of this editorial argues. Although current practice effectively screens for a number of diseases, it does not prevent all transfusion-transmitted infections (TTIs), nor does it entirely prevent transfusion-related sepsis. Pathogen inactivation addresses these issues and eliminates the need for irradiation of blood components, thus removing the risk of graft-versus-host disease. Pathogen inactivation should be more widely adopted, with the additional costs weighed against improvements in blood safety, the author writes. However, current interest in this technology does not address noninfectious blood transfusion hazards and focuses on use in developed countries.

As the HIV epidemic in South Africa escalated in the late 1990s, so did HIV infections in the nation's blood supply, which was an indication of a significant number of new infections undetected by an antibody test (window-period infections). In response, in 1999 the National Blood Service closed blood donation sites in high-prevalence areas, implemented an oral questionnaire about HIV risk behaviors for donors, and began triaging donated products based on risk profiling, issuing the safest products first. As a result, HIV prevalence in blood donations fell from a peak of 0.26 percent in 1998 to 0.05 percent in 2003. First-time donors were significantly more likely to have HIV than repeat donors. After the new screening protocol was implemented, the proportion of first-time donors decreased significantly between 1999 and 2000 and 2001 and 2002. Furthermore, the prevalence of HIV among these donors decreased significantly, from 1.08 percent in 1999 to 2000 to 0.59 percent in 2001 to 2002. The authors estimate a 24 percent reduction from 1999 to 2001/2002 in risk of collecting a unit of blood infected with HIV from a donor in the window period. Collection policies will continue to be adjusted over time to ensure the continued safety of the South African blood supply.

The equipment-dependent western model of safe blood procurement is inefficient and unaffordable in small-scale settings in Africa. This paper proposes predonation screening for hepatitis B, hepatitis C, and HIV by rapid testing, followed by nucleic acid testing (NAT) on batches of donated samples, as an affordable means of improving blood safety. As well as being cheaper than traditional screening of donated blood, this method also enables infected donors to be referred for further care, in itself a public health benefit. A study in Ghana found that in high endemic areas, such testing is effective and may reduce the cost of ensuring safe blood supply.

This paper highlights the disparity between developed countries that can rely on high-performance technology to guarantee safe supplies of donated blood and resource-poor countries facing many obstacles to safe blood provision. Namely those obstacles include limited budget; the high prevalence of HIV, hepatitis B, and hepatitis C; and factors adversely affecting retention of voluntary donors. Developing countries should use rapid tests before blood donation rather than striving for a technology-heavy solution. However, developing countries have special requirements of such tests in terms of reagent formulation and test design to compensate for the lack of sensitivity of dipstick tests compared to enzyme immunoassay screening.

This paper describes a novel model to estimate the proportion and number of people infected with HIV through blood transfusion in the San Francisco Bay area before the introduction of HIV antibody screening in 1985. The model relied on data on identified HIV-positive blood donations, the prevalence of HIV among homosexual and bisexual men in San Francisco from 1978 to 1984, donation rates to a blood center over the same period, and the outcome from the tracing of recipients of seropositive transfusions. The authors found the risk of infection was higher than previously estimated, and they underline the importance of donor education and self-exclusion to protect blood supply.

This section of the AABB's website is targeted to potential blood donors. In non-technical language, it explains why blood donations are needed and why people become blood donors. It answers questions commonly asked by potential blood donors, including information on the process of blood donation and on the meaning of donor deferral. There is a step-by-step guide to the blood donation process from predonation screening to postdonation care. There are also links to the AABB's Donor History Task Force donor history questionnaires and guidance documents. For U.S. residents, there is a blood bank locator tool and information on how to organize a blood drive.

The AABB's education and training materials comprise four categories: web-based courses, training manuals, slide presentations, and general resources. The web-based courses on basic cell therapy, transfusion-related acute lung injury, and the Code of Good Manufacturing Practice in the Transfusion Service are fee-based with individual and institutional rates. The other materials are all available free of charge. There are manuals on donor services training and blood administration as well as resources on a variety of topics of relevance to blood bank professionals.

These design guidelines can be used to help countries develop blood services facilities. They can be used not just in the design of purpose-built facilities, but also in the renovation of existing buildings and to assess layout to improve work patterns. The guidelines are in two parts, covering function and design. The functional brief covers the role and function of a blood center, issues that should be considered in its design, the operation and function of units, and how much space is required based on various average workloads. The design brief describes physical performance and engineering services requirements of the building itself.

The WHO website section on blood safety brings together a plethora of guidance documents, training materials, and tools from the WHO's Blood Transfusion Safety team to explain why blood safety is important and how it can be achieved. Key resources include recommendations on screening blood for transmissible infections, universal access to safe blood transfusion, and guidelines on the design of blood centers. The site's documentation center houses forms and reports related to all aspects of blood safety, including questionnaires and reports from the Global Database on Blood Safety. Related information from within and outside WHO is also accessible through this site.

This publication comprises 17 original articles that are, in effect, chapters of a training manual. The publication is targeted at students and inexperienced readers, rather than with the expert in mind. Written by specialists in blood transfusion technology, it covers the entire transfusion chain. Chapters begin with learning objectives, conclude with a content summary, and can be studied individually or read as a coherent whole. There are copious illustrations and a comprehensive glossary. Although the content is wide-ranging, it does not cover recent technological advances such as cord blood banking and stem cell production.

International Federation of Red Cross and Red Crescent Societies. (2007).

Donor recruiters can use the seven modules that make up this manual for self-study training purposes. Starting with basic information about blood safety, the manual covers donor education and social marketing strategies and the process of bringing in and serving donors. There is also a module on building partnerships and another specifically covering recruitment of youth donors. The final module covers human resources, research, and forward planning. Each module includes a list of learning objectives and activities to help reinforce the learning process. Modules can be downloaded separately or as one publication.

This website provides an overview of the C-Change project, a communication project that aims to influence change in social norms to improve health behaviors. In addition to providing information about their approach, readers can find program information for 15 countries worldwide. The project's focus areas include strengthening local capacity for communication for social change, family planning, HIV prevention, malaria, and gender equity.

C-Picks is an online magazine that includes resources on social and behavior change communication, including HIV prevention efforts. These selected resources include evaluations, implementation experiences, strategic guidance, and other tools and resources. Readers can browse the archives by date, technical area, country, or region. HIV-related topics include male circumcision, multiple and concurrent partnerships, and integration with family planning/reproductive health services.